A New Strategy To Construct Acyclic Nucleosides Via Ag(Ⅰ)-catalyzed Addition Of Pronucleophiles To9-allenyl-9H-purines

Many modified bases of nucleoside and nucleotide derivatide play a very important rolein antiviral and anticancer activities. At present the vast majority of antiviral drugs whichhave already in the market or put into clinical are nucleoside drugs. These unnaturalnucleosides were employed to treat diseases by incorporating into DNA chains to terminatethe extending of DNA chains. As research continues, nucleoside drugs were found with highin mammalian toxicity and high in drug tolerance，so we need to develop new drugs with lowcytotoxicity and low drug tolerance. The discovere of acyclic nucleoside could provide us anefficient solution. Acyclic nucleosides, compared with tradtion nucleoside drugs with low inmammalian toxicity and low in drug tolerance. In recent years with more and more scienatistcontinue research on acyclic nucleoside, and provide human a new era for antiviral therapy.Acyclic nucleoside and nucleotide has been an unique role in antiviral and anticanceractivities, and attracted many chemists’ interest. However, the former report synthesisprocesses of the acyclic nucleoside have some drawbacks, such as multi steps, low yields andhard to get chiral source. So it is significant to develop an efficient and economical syntheticmethod of carbolic analogues.A new strategy to construct acyclic nucleosides with diverse side chains was developed.With Ag(I) salts as catalysts, the hydrocarboxylation, hydroamination, and hydrocarbonationreactions proceeded well, affording acyclic nucleosides in good yields (41examples,60-98%yields). Meanwhile, these reactions exhibited high chemoselectivities and E-selectivities.We also studied an efficient synthetic method for the preparation of chiral acyclicnucleosides by ring-opening reaction between nucleoside bases and Sharpless epoxidtionproducts. This approach provide acyclic nucleosides with two contiguous stereocenters with good yields, excellent diatereo-(>99:1dr) and enantioselectivities (up to>99:1ee). It could bepotentially of great importance in medicinal chemistry.This paper opens up a new synthetic route acyclic nucleoside, synthesis of acyclicnucleosides with diverse side chains. Their structures were conformed by1H NMR,13C NMR,35P NMR,19F NMR and HRMS.